The aims of the project are (a) to determine the extent of involvement of the secretory immune system in sicca syndrome (SS) and rheumatoid arthritis (RA), and (b) to determine the relationship between disorders of the secretory immune system and humoral immunity in the above diseases. Secretions easily accessible from patients (salivary, nasal and lacrimal) as well as secretions obtained at the time of endoscopy or surgery will be tested for autoantibody activity by solid-phase radioimmunoassays or ELISA. The spectrum and activity of antibodies to human IgG and extractable nuclear antigens will be compared in serum and secretions. To determine whether secretory and humoral antibodies are derived from the same clone of B cells, the antibodies will be immunopurified from affinity columns and their spectrotypes compared by isoelectric focusing in agarose. The idiotypic determinants of the antibodies will also be compared by radioimmunoassay inhibition studies. The long-term objectives of this study are to define the nature of involvement of the secretory immune system in SS and RA such that the hypothesis that these disorders arise from a mucosal stimulus can be evaluated. If the findings in (a) above support such a hypothesis, efforts will be directed to identification of the mucosal stimulus. This, in turn, would provide a totally new challenge in terms of treatment and prevention.